Project Summary We propose a novel way of reconstructing medical images rooted in deep learning and computer vision that models the process how human radiologists are using years of experience from reading thousands of cases to recognize anatomical structures, pathologies and image artifacts. Our approach is based on the novel idea of a variational network, which embeds a generalized compressed sensing concept within a deep learning framework. We propose to learn a complete reconstruction procedure, including filter kernels and penalty functions to separate between true image content and artifacts, all parameters that normally have to be tuned manually as well as the associated numerical algorithm described by this variational network. The training step is decoupled from the time critical image reconstruction step, which can then be performed in near-real-time without interruption of clinical workflow. Our preliminary patient data from accelerated magnetic resonance imaging (MRI) acquisitions suggest that our learning approach outperforms the state-of-the-art of currently existing image reconstruction methods and is robust with respect to the variations that arise in a daily clinical imaging situation. In our first aim, we will test the hypothesis that learning can be performed such that it is robust against changes in data acquisition. In the second aim, we will answer the question if it is possible to learn a single reconstruction procedure for multiple MR imaging applications. Finally, we will perform a clinical reader study for 300 patients undergoing imaging for internal derangement of the knee. We will compare our proposed approach to a clinical standard reconstruction. Our hypothesis is that our approach will lead to the same clinical diagnosis and patient management decisions when using a 5min exam. The immediate benefit of the project is to bring accelerated imaging to an application with wide public-health impact, thereby improving clinical outcomes and reducing health-care costs. Additionally, the insights gained from the developments in this project will answer the currently most important open questions in the emerging field of machine learning for medical image reconstruction. Finally, given the recent increase of activities in this field, there is a significant demand for a publicly available data repository for raw k-space data that can be used for training and validation. Since all data that will be acquired in this project will be made available to the research community, this project will be a first step to meet this demand.